Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 34411 | 103456;103457;103458 | chr2:178533384;178533383;178533382 | chr2:179398111;179398110;179398109 |
| N2AB | 32770 | 98533;98534;98535 | chr2:178533384;178533383;178533382 | chr2:179398111;179398110;179398109 |
| N2A | 31843 | 95752;95753;95754 | chr2:178533384;178533383;178533382 | chr2:179398111;179398110;179398109 |
| N2B | 25346 | 76261;76262;76263 | chr2:178533384;178533383;178533382 | chr2:179398111;179398110;179398109 |
| Novex-1 | 25471 | 76636;76637;76638 | chr2:178533384;178533383;178533382 | chr2:179398111;179398110;179398109 |
| Novex-2 | 25538 | 76837;76838;76839 | chr2:178533384;178533383;178533382 | chr2:179398111;179398110;179398109 |
| Novex-3 | None | None | chr2:None | chr2:None |
Information
Reported SAVs
| SNV | RS | DUET |
PolyPhen-2 |
Condel |
Rhapsody |
REVEL |
MVP |
Source |
MAF |
Disease |
Zygosity |
Site annotation |
mCSM PPI |
Predicted PPI site |
Comments |
AFR |
AMR |
AMS |
ASJ |
EAS |
EUR |
FIN |
MDE |
NFE |
SAS |
OTH |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/N | rs72629784  |
-2.402 | 0.996 | D | 0.631 | 0.687 | 0.889221403107 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.66E-05 | 0 |
| I/N | rs72629784 |
-2.402 | 0.996 | D | 0.631 | 0.687 | 0.889221403107 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 4.41E-05 | 0 | 0 |
| I/N | rs72629784 |
-2.402 | 0.996 | D | 0.631 | 0.687 | 0.889221403107 | gnomAD-4.0.0 | 3.71853E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.08536E-06 | 0 | 0 |
Saturation Mutagenesis
SAV |
AlphaMissense (IC) |
AlphaMissense Class (IC) |
AlphaMissense (N2AB) |
AlphaMissense Class (N2AB) |
mCSM |
mCSM class |
PolyPhen-2 |
PolyPhen-2 Class |
Rhapsody |
Rhapsody Class |
Condel |
Condel Score |
Site annotation |
mCSM PPI |
Predicted PPI site |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.9362 | likely_pathogenic | 0.9118 | pathogenic | -2.006 | Highly Destabilizing | 0.863 | D | 0.455 | neutral | None | None | None | None | I |
| I/C | 0.9441 | likely_pathogenic | 0.9338 | pathogenic | -1.224 | Destabilizing | 0.999 | D | 0.515 | neutral | None | None | None | None | I |
| I/D | 0.9856 | likely_pathogenic | 0.984 | pathogenic | -1.923 | Destabilizing | 0.997 | D | 0.619 | neutral | None | None | None | None | I |
| I/E | 0.9589 | likely_pathogenic | 0.9518 | pathogenic | -1.738 | Destabilizing | 0.997 | D | 0.623 | neutral | None | None | None | None | I |
| I/F | 0.521 | ambiguous | 0.4475 | ambiguous | -1.235 | Destabilizing | 0.976 | D | 0.486 | neutral | N | 0.521978546 | None | None | I |
| I/G | 0.985 | likely_pathogenic | 0.9798 | pathogenic | -2.451 | Highly Destabilizing | 0.997 | D | 0.621 | neutral | None | None | None | None | I |
| I/H | 0.962 | likely_pathogenic | 0.9521 | pathogenic | -1.55 | Destabilizing | 0.999 | D | 0.617 | neutral | None | None | None | None | I |
| I/K | 0.916 | likely_pathogenic | 0.8991 | pathogenic | -1.342 | Destabilizing | 0.997 | D | 0.628 | neutral | None | None | None | None | I |
| I/L | 0.3922 | ambiguous | 0.3164 | benign | -0.749 | Destabilizing | 0.015 | N | 0.128 | neutral | N | 0.490519488 | None | None | I |
| I/M | 0.2493 | likely_benign | 0.2205 | benign | -0.719 | Destabilizing | 0.976 | D | 0.487 | neutral | D | 0.528019084 | None | None | I |
| I/N | 0.8777 | likely_pathogenic | 0.8641 | pathogenic | -1.637 | Destabilizing | 0.996 | D | 0.631 | neutral | D | 0.527642647 | None | None | I |
| I/P | 0.9797 | likely_pathogenic | 0.9769 | pathogenic | -1.148 | Destabilizing | 0.997 | D | 0.621 | neutral | None | None | None | None | I |
| I/Q | 0.9433 | likely_pathogenic | 0.9309 | pathogenic | -1.559 | Destabilizing | 0.997 | D | 0.622 | neutral | None | None | None | None | I |
| I/R | 0.9 | likely_pathogenic | 0.8796 | pathogenic | -1.052 | Destabilizing | 0.997 | D | 0.631 | neutral | None | None | None | None | I |
| I/S | 0.9353 | likely_pathogenic | 0.9215 | pathogenic | -2.288 | Highly Destabilizing | 0.988 | D | 0.571 | neutral | D | 0.530483386 | None | None | I |
| I/T | 0.8656 | likely_pathogenic | 0.8112 | pathogenic | -1.956 | Destabilizing | 0.92 | D | 0.505 | neutral | N | 0.486052086 | None | None | I |
| I/V | 0.1857 | likely_benign | 0.1339 | benign | -1.148 | Destabilizing | 0.021 | N | 0.12 | neutral | N | 0.502213775 | None | None | I |
| I/W | 0.9517 | likely_pathogenic | 0.9442 | pathogenic | -1.421 | Destabilizing | 0.999 | D | 0.671 | neutral | None | None | None | None | I |
| I/Y | 0.8636 | likely_pathogenic | 0.8458 | pathogenic | -1.125 | Destabilizing | 0.997 | D | 0.534 | neutral | None | None | None | None | I |
Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.